A Family of Unconventional Deubiquitinases with Modular Chain Specificity Determinants

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Feb 25

PMID 29476094

Citations 76

Authors

Thomas Hermanns

Christian Pichlo

Ilka Woiwode

Karsten Klopffleisch

Katharina F Witting

Huib Ovaa

Ulrich Baumann

Kay Hofmann

Affiliations

Soon will be listed here.

Abstract

Deubiquitinating enzymes (DUBs) regulate ubiquitin signaling by trimming ubiquitin chains or removing ubiquitin from modified substrates. Similar activities exist for ubiquitin-related modifiers, although the enzymes involved are usually not related. Here, we report human ZUFSP (also known as ZUP1 and C6orf113) and fission yeast Mug105 as founding members of a DUB family different from the six known DUB classes. The crystal structure of human ZUFSP in covalent complex with propargylated ubiquitin shows that the DUB family shares a fold with UFM1- and Atg8-specific proteases, but uses a different active site more similar to canonical DUB enzymes. ZUFSP family members differ widely in linkage specificity through differential use of modular ubiquitin-binding domains (UBDs). While the minimalistic Mug105 prefers K48 chains, ZUFSP uses multiple UBDs for its K63-specific endo-DUB activity. K63 specificity, localization, and protein interaction network suggest a role for ZUFSP in DNA damage response.

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